Environmental, Familial, and Leukocyte-Associated Variance of Methylation Quantitative Trait Loci in the Human Genome

• Activity Number: 17
• Type: Topic Contributed
• Date/Time: Sunday, August 3, 2014 : 2:00 PM to 3:50 PM
• Sponsor: International Chinese Statistical Association
• Author(s): Liming Liang*+
• Companies: Harvard School of Public Health
• Keywords: methylation ; heritability ; cell specific effect ; epigenetic variation

Abstract

The determinants of epigenetic variation in the human genome are not systematically understood. We therefore carried out segregation analyses of methylation quantitative traits (meQTL) at 27,000 loci (representing 14,500 CpG islands (CGI)) in DNA from peripheral blood leukocytes (PBL) from two panels of nuclear families. Major components of variation in meQTL across all loci included general environment (71% of variation), the shared family environment (9%), age (6%) and sex (4%). We saw strong genetic influences (meSNPs) on methylation status at 10% of loci. After accounting for SNP effects, at most 4% of meQTL variation could be transmitted from parents to children. We identified reproducible leukocyte type specific methylation patterns, and showed an overall cell-specific contribution to variation in methylation of 6%. The results show that meQTL in DNA from PBL capture genomic responses to factors that are largely environmentally derived, so that genome-wide mapping of meQTL may directly inform on mechanisms of environmentally driven diseases. We provide a reference database that identifies meSNPs and meQTL as well as VC estimates for age, sex, and cell count for each locus.